Abstract: AIM: To observe the effect of pioglitazone on serum MMP-9 concentration and expression of peripheral monocyte MMP-9 in diabetic rats. METHODS: Forty Wistar rats were randomly divided into five groups: control group, diabetes group and three pioglitazone groups of 5, 10, 20 mg/(kg·d), respectively. The rat diabetic model was made by IP injection of streptozocin. After the model was successfully made, rats in pioglitazone group were treated with pioglitazone ［5, 10 or 20 mg/(kg·d)×28 days］JP by gavage and rats in the control group and diabetes group were treated with normal saline. Concentrations of serum MMP-9 were detected by ELISA. Expression of peripheral monocyte MMP-9 was measured by RT-PCR and Western blot. RESULTS: The concentration of serum MMP-9 was dose-dependently lowered by pioglitazone treatment. Expression of peripheral monocyte MMP-9 was also down-regulated by pioglitazone treatment. CONCLUSION: Results indicate that pioglitazone may have some protective cardiovascular effect in addition to a hypoglycemic effect.